Red blood cells covalently bound with polymers

• US 6,942,859 B2
• Filed: 11/05/2001
• Issued: 09/13/2005
• Est. Priority Date: 03/13/1998
• Status: Expired due to Fees

• Current Assignee: University of Southern California
• Original Assignee: University of Southern California
• Inventors: Fisher, Timothy C., Armstrong, Jonathan K.
• Primary Examiner(s): Naff, David M.
• Application Number:
  US10/012,726
• Publication Number:
  US 20020141976A1
• Time in Patent Office: 1,408 Days
• Field of Search: 424/93.7, 424/93.73, 435/2, 435/180, 435/325, 435/372, 530/385
• US Class Current: 424/93.7
• CPC Class Codes: A01N 1/02 Preservation of living parts
• CPC Class Codes: A01N 1/0221 Freeze-process protecting agents, i.e. substances protecting cells from effects of the physical process, e.g. cryoprotectants, osmolarity regulators like oncotic agents
• CPC Class Codes: A61K 35/18 Erythrocytes haemoglobin A61K38/42

Abstract

Living cells modified at their surface with specially selected polymers are disclosed. A simple method to covalently attach specially selected PEG derivatives to the surface of RBC in aqueous media under mild conditions is a preferred example. The selected PEG-modification dramatically reduced aggregation and low shear viscosity of RBC resuspended in autologous plasma, and inhibited RBC agglutination by blood group-specific antibodies. The morphology and deformability of the PEG-treated cells were unaltered. The PEG coating of the RBC surface is applicable to the treatment of a variety of diseases characterized by vaso-occlusion or impaired blood flow, e.g., myocardial infarction, shock, and sickle cell disease.

Claims

1. A physiologically compatible solution for infusion comprising:

red blood cells covalently labelled with a copolymer of oxyethylene and oxypropylene.

2. The solution of claim 1 wherein the copolymer has a molecular weight between approximately 2,000 and 50,000.

3. The solution of claim 1 wherein the copolymer is a block copolymer.

4. The solution of claim 1 wherein the copolymer is a tri-block copolymer.

5. The solution of claim 4 wherein the tri-block copolymer is a poloxamer.

6. The solution of claim 5 wherein the poloxamer is poloxamer 108.

7. The solution of claim 5 wherein the poloxamer is poloxamer 188.

8. The solution of claim 5 wherein the poloxamer is poloxamer 288.

13. A method to treat a pathological condition comprising:

identifying a disorder treatable by altering blood viscosity, and

altering blood viscosity by administering the composition of any of claims 1-12.

14. The method of claim 13 wherein the condition is selected from the group consisting of sickle cell disease, myocardial infarction, shock, ischemic vascular disorder, a peripheral vascular disease.

15. The method of claim 14 further comprising administering a thrombolytic agent.

9. A physiologically compatible solution for infusion comprising:

red blood cells covalently labelled with a copolymer of oxyethylene and oxybutylene.

10. The solution of claim 9 wherein said copolymer is a block copolymer.

11. The solution of claim 10 wherein said copolymer is a tri-block copolymer.

12. The solution of claim 11 wherein said tri-block copolymer has a molecular weight between approximately 4,000 and 50,000.